■4 1S 



CHAPTER 32 



Present Genes 



Myoglobin Gene a y F p 8 Ai 



Ancestral Gene 



FIGURE 32-9. Gene duplication and intragenic 

 mutation hypothesis for the molecular evolu- 

 tion of myoglobin and hemoglobin. 



which specify hemoglobin are rare, and be- 

 cause the linkage maps of man are so in- 

 complete, it is difficult to learn the precise 

 relative positions of the various nonalleles. 

 For the same reasons, it is difficult to study 

 the allelism of hemoglobin mutants which 

 affect the same chain. 



* Molecular Evolution of Hemoglobin !l 



Present-day myoglobin, a protein in muscle, 

 is composed of a single chain of 155 amino 

 acids which partly forms a right-handed a 

 helix and carries a single heme group on its 

 surface. When the amino acid sequence of 

 myoglobin is compared with that of the a 

 or (3 chain of hemoglobin, a large number 

 of differences are found. After accounting 

 for the difference in chain length, however, 

 a number of places still remain where the 

 same amino acid occurs on both types of 

 chain. These similarities probably explain 

 why both types of chain have the same 

 three-dimensional arrangement. Though it 



•'See V. M. Ingram (1961). and C. B. Anfinsen 

 (1959). 



is possible that some, If not all. of these 

 similarities are due to convergent evolution 

 by unrelated genes, we can postulate as the 

 basis for the observed chain similarities that 

 the genes specifying these present-day chains 

 have a common gene ancestor (Figure 32- 

 9). 



According to this hypothesis, an ancestral 

 gene, a, must have been duplicated in the 

 genome by one of the mechanisms discussed 

 in Chapter 12, since present-day species 

 have separate loci for the specification of 

 myoglobin and hemoglobin. Subsequent 

 mutations of one gene could give rise to the 

 present-day locus for myoglobin production, 

 whereas mutations of the other gene could 

 give rise to the ancestral locus for hemo- 

 globin chains. Such mutations might re- 

 sult in the addition or — more likely — the 

 removal or substitution of amino acids sin- 

 gly or in groups. This common-origin hy- 

 pothesis is supported by the finding that the 

 hemoglobin of the lamprey consists of a 

 single polypeptide chain with a molecular 

 weight of about 17,000 and that hagfish he- 

 moglobin appears to be a similar monomer 

 or possibly a dimer with a molecular weight 

 of about 34,000. 



Since all known hemoglobins of verte- 

 brates, except for the lamprey, have a he- 

 moglobin chain that starts with a Val-Leu 

 sequence, they may all be products of mu- 

 tants of a. Accordingly, it is suggested that 

 the ancestral gene for hemoglobin is a and 

 that after a arose, it mutated to an allele 

 whose polypeptide product could form a 

 dimer, since dimerization enhances a's ef- 

 ficiency as an oxygen carrier. Suppose, 

 next, that the a locus became duplicated 

 and that one of the resultant loci mutated 

 to y, which produced y chains, which, in 

 turn, formed not only dimers but also te- 

 tramers with the a dimers. The tetramer 

 would be a fetal-type hemoglobin a 2 y2. Te- 

 trameric hemoglobin is presumably more ef- 

 ficient than dimeric hemoglobin. 



